Abstract 1588P
Background
G-CSF has proven efficacy for CIN prevention, however, it is relatively ineffective in the 1st week of the chemo cycle due to its late onset mechanism of action (MoA) (Blayney, ASCO 2022). The novel CIN-preventive agent plinabulin (plin) protects against CIN within 24 hrs by protecting bone marrow GMP stem cells (Blayney, ASH 2021). Plin combined with pegfilgrastim has superior CIN prevention vs pegfilgrastim alone (Blayney, ASCO 2021). Here we further evaluate plin’s protective effects on GMPs.
Methods
Peripheral blood counts for mature (segmented) & immature neutrophils, WBCs, RBCs and platelets were obtained from LabCorp. The blood counts were analyzed before and 24 hrs after chemo administration w/o (control; N=198) or w/ plin (N=298). Data was obtained from the CIN phase 2/3 plin trials (1) PROTECTIVE-1 (NCT03102606) w/ docetaxel 75 mg/m2 in pts with NSCLC, breast cancer (BC), prostate cancer and (2) PROTECTIVE-2 (NCT0329457) w/ docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (TAC) in early-stage BC. The plin dose was 20 mg/m2 or 40 mg fixed and given as a single IV dose, 30 mins after chemo on Cycle 1 Day 1 (C1D1).
Results
Pre dose (C1D1), the proportion of pts with an immature count value >0 was ∼0, for both plin and control arms. At 24 hrs post-chemo, pts with an immature neutrophil count >0 had significantly increased w/ plin but not w/ the control. The proportion of pts with immature cells from all other WBCs and RBCs was ∼0 at pre- or post-chemo dose w/ or w/o plin. ANC w/ and w/o plin were comparable at pre-dose C1D1 but was significantly (p<0.001) higher at 24 hrs post-chemo dose w/ plin vs control. Table: 1588P
| Proportion of pts with: | Pre-Dose C1D1 Plin N (%) | Pre-Dose C1D1 Control N (%) | p-value | 24 hrs Post- Plin N (%) | 24 hr Post- Control N(%) | p-value |
| Promyelocytes | 0 (0) | 0 (0) | NA | 2 (0.7) | 0 (0) | 0.25 |
| Myelocytes | 1 (0.4) | 1 (0.5) | 0.8 | 23 (7.7) | 0 (0) | <0.0001 |
| Metamyelocytes | 1 (0.4) | 1 (0.5) | 0.8 | 20 (6.7) | 0 (0) | 0.0002 |
| Bands | 11 (3.7) | 9 (4.5) | 0.6 | 21 (7.0) | 2 (1.0) | 0.0017 |
Conclusions
Plin has rapid (within 24 hrs) protection of GMP progenitor stem cells based on an evaluation of peripheral immature and mature neutrophil counts. This finding may have clinical relevance for pts in need of rapid CIN prevention, since G-CSF has late onset MoA with CIN protection occurring after week 1.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
BeyondSpring Pharmaceuticals, Inc.
Funding
BeyondSpring Pharmaceuticals, Inc.
Disclosure
D. Blayney: Financial Interests, Personal, Advisory Role: BeyondSpring Pharmaceuticals, Inc.. R. Mohanlal: Financial Interests, Personal, Full or part-time Employment: BeyondSpring Pharmaceuticals, Inc.. L. Huang: Financial Interests, Personal, Full or part-time Employment: BeyondSpring Pharmaceuticals, Inc..